In this review, the authors discuss the underlying mechanisms of action of histone deacetylase inhibitors in multiple myeloma biology and analyze the future clinical implications for patients. Harada T, Hideshima T, & Anderson KC. Int J Hematol 2016; 104: 300–309. doi:10.1007/s12185-016-2008-0

This stimulates the catalytic activity of PARP1, which results in the synthesis of PAR chains on itself and on histone and non-histone proteins 15, 18, 19 .

The histone deacetylase inhibitor vorinostat was representative of clinical results, with no objective responses observed in either 8/8 ALL PDXs 48 or 6/6 pediatric leukemia patients in a Phase I trial. 104 Likewise, 2/2 ALL patients did not respond to vorinostat in an adult Phase I trial. 105 Similarly, the immunomodulatory agent lenalidomide showed no activity across the ALL PDX panel and had no clinical effect against adult ALL cases in a Phase I trial. 106 The stringency of PPTP testing criteria highlighted the broad lack of efficacy of kinase inhibitors as single agents.

Additionally, TDP1, which is overexpressed in rhabdomyosarcoma cell lines, displays SDL with the inhibition of histone deacetylases 18 .

More recently, the landscape of MM therapy continues to expand further with the approval of next generation proteasome inhibitors and immunomodulatory agents as well as the recent approval of new drugs with novel mechanisms of action including monoclonal antibodies and histone deacetylase inhibitors. 15, 16, 17  With the rapid changes in MM therapy, our goal with this review is to analyze the current literature and provide recommendations for maintenance therapy in MM, primarily with lenalidomide and bortezomib.

As many as 90% of TNBCs that persist after chemotherapy contain alterations in pathways that can be targeted with agents currently under clinical investigation 91, such as PARP inhibitors, PI3K inhibitors, MEK inhibitors, heat shock protein 90 (HSP 90) inhibitors and histone deacetylase (HDAC) inhibitors (Fig. 2).

On the basis of data showing valproic acid (VPA) acts as a potent histone deacetylase (HDAC) inhibitor, Tassara and colleagues 32  examined the therapeutic potential of the addition of VPA to standard induction therapy plus ATRA in patients with AML.

This review summarizes data from key clinical trials of poly [ADP-ribose] polymerase inhibitors and discusses how to integrate these agents into the current treatment landscape of ovarian cancer.  Nat Rev Clin Oncol  2017;14: 284–296. doi:10.1038/nrclinonc.2016.191

In this paper, key clinical trials of poly(ADP-ribose) polymerase (PARP) inhibitors are summarized, and the place of the PARP inhibitors in the treatment of ovarian cancer is explored, with a focus on the importance of testing for BRCA and other biomarkers. Nat Rev Clin Oncol  2017;14:284–296. doi:10.1038/nrclinonc.2016.191

NCT02077959, phase I/II Lenalidomide Small molecules and signaling pathway inhibitors Vemurafenib BRAF V600E i.v.

Examples include drugs that inhibit bromodomain histone readers, 143, 144 histone demethylases 145 and histone deacetylases, 146 which have been shown to be effective in experimental models of ALL.